'New treatment opportunities rise for acquired hemophilia A'

Jin Seok Kim, Professor of Hematology at Severance Hospital

Limitations of bypass therapy lead to frequent rebleeding... the only Factor VIII replacement therapy is introduced to the scene

One year after Obizur reimbursement…. personalized treatment based on patient monitoring reduces burden on medical staff

Reimbursement is currently limited and based on antibody titer criteria… Urgent need for systemic improvements that base the criteria on bleeding severity

There is an extremely rare bleeding disorder that affects one in every 100,000 people.

 

It is acquired hemophilia A, a condition in which healthy individuals experience unexplained bruising and severe bleeding throughout the body.

 

Until recently, there were limited treatment options available for emergencies, causing significant challenges for medical staff in controlling the patients’ bleeding.

 

Episodes.

 

In this context, the introduction of “Obizur ( susoctocog alfa), a blood coagulation factor VIII agent” as the first treatment for adult acquired hemophilia A in Korea last year, followed by its reimbursement, has brought about major changes in the treatment environment.

 

Dailpharm met with Jin Seok Kim, Professor of Hematology at Severance Hospital, to discuss the changes brought about by the introduction of Obizur in clinical practice and the challenges that remain.

 

Unexplained autoimmune bleeding…delayed diagnosis can be fatal

Jin Seok Kim, Professor of Hematology at Severance Hospital

While congenital hemophilia is a bleeding disorder caused by genetic factors, acquired hemophilia A occurs when antibodies against blood coagulation factor VIII (Factor VIII) are produced due to an autoimmune response.

 

This rare disease causes bleeding by inhibiting the function of Factor VIII, and its symptoms appear similar to those of congenital hemophilia, such as bruising or bleeding.

 

Professor Kim explained, “While acquired hemophilia can arise secondary to malignant tumors, autoimmune diseases, medications, or pregnancy, approximately 50% of cases are reported as idiopathic, meaning they occur without a clear underlying cause.

 

Given its rarity and unfamiliarity, patients may feel overwhelmed, but some cases can progress to severe bleeding requiring emergency treatment, making prompt diagnosis critically important.” According to statistics from Western countries, the incidence is approximately 1 in 1 million people, which translates to about 50 cases per year in South Korea based on its population.

 

However, the actual number of reported cases in the country is much lower, estimated at around 20 per year.

 

Professor Kim added, “Since acquired hemophilia A is such a rare disease, general medical staff are often unaware of it, leading to delayed diagnosis.

 

When treating patients with unexplained generalized bleeding or atypical bleeding patterns, it is crucial to actively work with a hematologist.” The primary goal of treatment for acquired hemophilia A is to stop life-threatening bleeding while removing antibodies to prevent recurrence quickly.

 

This requires concurrent hemostatic therapy and immunosuppressive therapy, a process that is highly complex and challenging.

 

Professor Kim explained, “Acquired hemophilia A requires not only hemostasis but also immunosuppressive therapy to remove autoantibodies, which can make treatment complex and risky.

 

Highly potent immunosuppressants such as steroids and cyclophosphamide must be used to remove antibodies, but in elderly patients, the risk of severe infections such as pneumonia and sepsis is high, and death from infection during treatment is not uncommon.” Intoduction of Obizur changes the paradigm of acquired hemophilia A treatment There were also difficulties in selecting emergency hemostatic agents.

 

Prior to the introduction of Obizur, bypassing agents were the standard hemostatic treatment for acquired hemophilia A.

 

These are medications that bypass the deficient Factor VIII in the body and help form fibrin clots through an alternative pathway.

 

In South Korea, recombinant activated Factor VII (rFVIIa, eptacog alfa) was primarily used as first-line therapy.

 

rFVIIa activates blood clotting factors in a short time to induce temporary hemostasis, but it has the limitation of a very short duration of action (half-life) of approximately 2 hours.

 

Professor Kim mentioned, “Due to its very short half-life of two hours, as well as the high cost of the drug and reimbursement limitations, it was difficult to adhere to the recommended dosing interval (two hours), resulting in insufficient hemostasis or recurrent bleeding in many cases.” In this situation, Obizur, which was reimbursed last year, is said to have brought a positive impact.

 

Obizur is a recombinant porcine sequence factor VIII (rpFVIII) drug developed to avoid cross-reactivity with human factor VIII autoantibodies.

 

It can replace factor VIII to achieve hemostatic effects and has a longer half-life of approximately 10 hours, enabling stable and sustained hemostatic management.

 

Professor Kim stated, “It has been just over a year since Obizur was introduced.

 

While we are still accumulating clinical evidence, experts on the front lines are clearly sensing positive changes.

 

Obizur is evaluated as having equivalent hemostatic efficacy and effectiveness to existing bypass therapies, but with the ability to monitor treatment responses more objectively, which is a key differentiator.” When using existing bypass therapies, decisions on dose reduction or treatment termination were based solely on the patient's clinical bleeding signs.

 

However, Obizur allows for objective determination of treatment dose and duration by measuring plasma factor VIII levels.

 

He explained, "Once bleeding is controlled, treatment can be discontinued early based on numerical confirmation, and conversely, additional doses can be administered if levels do not rise sufficiently, enabling personalized treatment.

 

This reduces unnecessary overdose and the risk of side effects such as thrombosis, and since only the optimal dose for each patient is used, the cost of treatment is also reduced.” Reimbursement standards still remain a barrier...

 

“Clinical judgment should be taken into account in reimbursement decisions” Although the treatment environment for acquired hemophilia A has improved significantly with the introduction of Obizur, practical constraints and remaining challenges still do exist.

 

One of the most notable issues is its health insurance reimbursement criteria.

 

Currently, under Korea’s reimbursement standards, only patients with antibody titers of 5 BU or higher are eligible for reimbursement for bypass agents or Obizur, which is the same as for congenital hemophilia patients.

 

However, experts believe that the current criteria, which require selecting medications based on antibody titers, are inappropriate for acquired hemophilia as there is a low correlation between antibody titers and bleeding severity.

 

Professor Kim stated, “Under the current reimbursement criteria, it is necessary to confirm the antibody titer before starting treatment and determine insurance coverage, which can lead to treatment delays or administrative burdens.

 

Additionally, the 5BU standard is not applied in any domestic or international treatment guidelines.” He further explained, “Even with low antibody titers, severe bleeding can occur in acquired hemophilia, so clinical manifestations may differ significantly even if test results are similar.

 

Therefore, it is necessary to improve the system to determine insurance coverage based on the patient's bleeding patterns and clinical judgment rather than quantitative criteria.” In addition, Professor Kim emphasized the need to prompt early diagnosis by raising disease awareness.

 

He explained, “Even if effective treatments exist, delayed diagnosis inevitably worsens prognosis, and ultimately, the success of treatment depends on how fast we diagnose the condition.

 

Since acquired hemophilia is a rare disease, the general medical staff have low awareness, leading to delayed initial diagnosis.

 

Improving disease awareness is essential to prevent deaths caused by severe bleeding in the early stages.”